PK of BV100 in Patients VABP Suspected or Confirmed to Be Due to CRAB

NCT05685615 | Completed Phase 2 DMC

• 1 other identifier: BV100-006
• Study Type: interventional
• Target: 39
• Locations: 3 countries
• Sites: 16

Brief Summary

A multicenter Phase 2 study to evaluate the pharmacokinetics, efficacy, and safety of intravenous BV100 combined with Polymyxin B in adult patients with VABP suspected or confirmed to be due to CRAB

Conditions

Ventilator Associated Pneumonia

Outcome Measures

Primary Outcomes (2)

• To investigate the pharmacokinetic (PK) properties of BV100 co administered with Polymyxin B during 7 to 14 days of treatment in patients with ventilator associated bacterial pneumonia (VABP)

  Maximum Observed Plasma Concentration (Cmax) of rifabutin

  14 days

• To investigate the pharmacokinetic properties of BV100 co administered with Polymyxin B during 7 to 14 days of treatment in patients with ventilator associated bacterial pneumonia (VABP)

  Area Under the Plasma Concentration-Time Curve (AUC) of rifabutin

  14 days

Secondary Outcomes (3)

• To assess the 28 day ACM rates of BV100 plus Polymyxin B compared to best available therapy (BAT)

  28 Days

• To assess the 14 day ACM rates of BV100 plus Polymyxin B compared to best available therapy (BAT)

  14

• To assess safety and tolerability of BV100 plus Polymyxin B compared to best available therapy (BAT)

  28 days

Study Arms (4)

BV100 (200 mg) plus Polymyxin B

EXPERIMENTAL

BV100 (200 mg q12h) infused over 2 hours plus Polymyxin B (12 500-15 000 IU/kg) infused over 1h

Drug: BV100 plus Polymyxin B

BV100 (300 mg) plus Polymyxin B

EXPERIMENTAL

BV100 (300 mg q12h) infused over 2 hours plus Polymyxin B (12 500-15 000 IU/kg) infused over 1h

Drug: BV100 plus Polymyxin B

Best Available Therapy

ACTIVE COMPARATOR

Best Available Antibiotic Therapy to Treat CRAB

Drug: BAT

Part B: BV100 plus BAT

EXPERIMENTAL

BV100 (300 mg q12h) infused over 2 hours plus Best Avaialble Therapy to Treat Colistin resistant CRAB

Drug: BAT

Interventions

BV100 plus Polymyxin B DRUG

Rifabutin for Infusion plus Polymyxin B for Injection

BV100 (200 mg) plus Polymyxin B; BV100 (300 mg) plus Polymyxin B

BAT DRUG

The best avaialble antibiotic therapy to treat CRAB

Also known as: Best Avaialble Therapy

Best Available Therapy; Part B: BV100 plus BAT

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients who meet all the following diagnostic and clinical criteria are eligible for the study:
• Provide written informed consent prior to any study related procedures not part of normal medical care. Surrogate consent/use of a legally authorized representative may be provided, if permitted by local country and institution specific guidelines. If a patient regains consciousness while in the study and, per the Investigator's judgment, the patient is able to read, assess, understand, and make his/her own decision to participate in the trial, the patient can agree to continue participation and the patient should be re consented, if required by local country and institution specific guidelines.
• Male or female patients ≥ and \< 80 years of age at the time of Informed Consent Form (ICF) signing with a body mass index (BMI) of \< 40 kg/m2 at the time of ICF signing.
• Hospitalized for ≥ 48 hours, intubated (via endo or nasotracheal tube, including tracheostomy patients) and receiving mechanical ventilation for ≥ 48 hours at the time of randomization, and with acute changes made in the ventilator support system to enhance oxygenation, as determined by arterial blood gas, or worsening PaO2/FiO2 ratio.
• All patients must have a chest radiograph or a lung CT scan within 48 hours prior to randomization showing the presence of new or progressive infiltrate(s) suggestive of bacterial pneumonia (based on Investigator's evaluation).
• Clinical findings to support diagnosis of VABP. At least 1 of the following must be documented to be present within 24 hours prior to randomization:
• Documented fever (oral ≥ 38.0 °C \[100.4 °F\] or a tympanic, temporal, rectal, or core temperature ≥ 38.3 °C \[101.0 °F\], axillary or forehead scanner ≥ 37.5 °C \[99.5 °F\]) OR
• Hypothermia (rectal/core body temperature ≤ 35.0 °C \[95.2 °F\]), OR
• Leukocytosis with total peripheral white blood cell count (WBC) ≥ 10 000 cells/mm3, OR
• Leukopenia with total peripheral WBC count ≤ 4500 cells/mm3.
• Acute Physiology and Chronic Health Evaluation (APACHE II) score between 8 and 30, inclusive, within 24 hours prior to randomization. Any data collected before ICF signature as part of a routine standard for patient care (e.g., laboratory values, Glasgow Coma Score, Acute Physiology Score \[APS\]) can be used for Screening Visit assessment, if applicable, without repeating the assessments.
• High probability of pneumonia due to A. baumannii, defined as follows:
• RDT, performed within 36 hours prior to randomization, using an acceptable respiratory sample (PBS, BAL, mini BAL, or ETA) positive for A. baumannii, OR
• A surveillance culture from a respiratory sample positive for A. baumannii within 72 hours prior to randomization.
• Part B specific:

You may not qualify if:

• Patients who meet any of the following criteria are not eligible to participate in this study:
• Known or suspected community acquired bacterial pneumonia or viral, fungal, or parasitic pneumonia.
• Sustained shock with persisting hypotension requiring vasopressors to maintain mean arterial pressure ≥ 60 mmHg
• Known or suspected allergy to polymyxin, rifabutin, BAT, or their excipients.
• Any of the following health conditions:
• Confirmed legionella infection (Legionella pneumophila pneumonia), Aspergillus spp. pneumonia (testing is not required)
• Candida spp. infection requiring systemic treatment
• Cystic fibrosis
• Known or suspected Pneumocystitis jiroveci pneumonia
• Known or suspected active tuberculosis
• Lung abscess
• Solid organ transplant within 6 months prior to randomization
• Pleural empyema
• Evidence of deep seated infection outside the respiratory tract, e.g., endocarditis, osteomyelitis.
• Known or suspected neuropathy or neuromuscular disease

Sponsors & Collaborators

• BioVersys AG: lead

Study Sites (16)

Academician Vakhtang Bochorishvili Clinic

Tbilisi, Georgia

Location

Eristavi National Center of Experimental and Clinical Surgery

Tbilisi, Georgia

Location

First University Clinic of Tbilisi State Medical University

Tbilisi, Georgia

Location

Gudushauri National Medical Center

Tbilisi, Georgia

Location

Malkhaz Katsiashvili Multiprofile Emergency Medicine Center

Tbilisi, Georgia

Location

Number 5 Clinical Hospital

Tbilisi, Georgia

Location

Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic

Tbilisi, Georgia

Location

General Hospital of Athens "Evangelismos"

Athens, Greece

Location

University General Hospital "Attikon"

Athens, Greece

Location

General University Hospital of Heraklion

Heraklion, Greece

Location

General Hospital of Larissa

Larissa, Greece

Location

University General Hospital of Larissa

Larissa, Greece

Location

General Hospital of Thessaloniki "Ippokratio"

Thessaloniki, Greece

Location

University of Debrecen Clinical Center

Debrecen, Hungary

Location

University Educational Hospital

Miskolc, Hungary

Location

Fejer County St. Gyorgy University Teaching Hospital

Székesfehérvár, Hungary

Location

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated

Interventions

Polymyxin B

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Polymyxins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Lipopeptides; Lipids; Antimicrobial Cationic Peptides; Peptides; Amino Acids, Peptides, and Proteins; Antimicrobial Peptides; Pore Forming Cytotoxic Proteins; Membrane Proteins; Proteins

Study Officials

• Lisa Husband, MD

  BioVersys SAS

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2023
• First Posted: January 17, 2023
• Study Start: April 20, 2023
• Primary Completion: November 1, 2024
• Study Completion: December 11, 2024
• Last Updated: January 14, 2025

Record last verified: 2023-11

Locations

GR (6); GE (7); HU (3)